Inhibition of Myogenic Tone in Rat Cremaster and Cerebral Arteries by SKA-31, an Activator of Endothelial KCa2.3 and KCa3.1 Channels

Ramesh C. Mishra, Heike Wulff, Michael A. Hill, Andrew P. Braun

Research output: Contribution to journalArticle

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Abstract

Endothelial KCa2.3 and KCa3.1 channels contribute to the regulation of myogenic tone in resistance arteries by Ca<sup>2+</sup>-mobilizing vasodilatory hormones. To define further the functional role of these channels in distinct vascular beds, we have examined the vasodilatory actions of the KCa channel activator SKA-31 in myogenically active rat cremaster and middle cerebral arteries. Vessels pressurized to 70 mm Hg constricted by 80-100 μm (ie, 25%-45% of maximal diameter). SKA-31 (10 μM) inhibited myogenic tone by 80% in cremaster and ∼65% in middle cerebral arteries, with IC<inf>50</inf> values of ∼2 μM in both vessels. These vasodilatory effects were largely prevented by the KCa2.3 blocker UCL1684 and the KCa3.1 blocker TRAM-34 and abolished by endothelial denudation. Preincubation with N<sup>G</sup> nitro l-arginine methyl ester (l-NAME, 0.1 mM) did not affect the inhibitory response to SKA-31, but attenuated the ACh-evoked dilation by ∼45%. Penitrem-A, a blocker of BK<inf>Ca</inf> channels, did not alter SKA-31 evoked vasodilation but did reduce the inhibition of myogenic tone by ACh, the BK<inf>Ca</inf> channel activator NS1619, and sodium nitroprusside. Collectively, these data demonstrate that SKA-31 produces robust inhibition of myogenic tone in resistance arteries isolated from distinct vascular beds in an endothelium-dependent manner.

Original languageEnglish (US)
Pages (from-to)118-127
Number of pages10
JournalJournal of Cardiovascular Pharmacology
Volume66
Issue number1
DOIs
StatePublished - Jul 23 2015

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Keywords

  • calcium-activated K+ channel
  • endothelium
  • myogenic tone
  • resistance artery
  • vasodilation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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